ERI1

Summary

ERI1 (exoribonuclease 1, HGNC:23994) is a protein-coding gene on chromosome 8p23.1, encoding 3’-5’ exoribonuclease 1 (Q8IV48). RNA exonuclease that binds to the 3’-end of histone mRNAs and degrades them, suggesting that it plays an essential role in histone mRNA decay after replication.

Enables 3’-5’ exonuclease activity. Involved in maturation of 5.8S rRNA. Located in cytoplasm and nucleolus.

Source: NCBI Gene 90459 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Hoxha-Aliu syndrome (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 69
• Clinical variants (ClinVar): 136 total — 3 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 102
• MANE Select transcript: NM_153332

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23994
Approved symbol	ERI1
Name	exoribonuclease 1
Location	8p23.1
Locus type	gene with protein product
Status	Approved
Aliases	3’HEXO
Ensembl gene	ENSG00000104626
Ensembl biotype	protein_coding
OMIM	608739
Entrez	90459

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000250263, ENST00000518663, ENST00000519292, ENST00000520332, ENST00000520684, ENST00000521844, ENST00000522258, ENST00000522612, ENST00000674098, ENST00000877111, ENST00000877112, ENST00000877113, ENST00000952041, ENST00000952042

RefSeq mRNA: 4 — MANE Select: NM_153332 NM_001354635, NM_001354636, NM_001354638, NM_153332

CCDS: CCDS5972

Canonical transcript exons

ENST00000250263 — 7 exons

Exon	Start	End
ENSE00001019499	9007970	9008148
ENSE00001019501	9002897	9003171
ENSE00002248622	9029792	9033338
ENSE00003462680	9020350	9020464
ENSE00003473739	9016322	9016405
ENSE00003625306	9018297	9018406
ENSE00003661393	9011542	9011752

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 93.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.3024 / max 199.4382, expressed in 1808 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87284	16.7788	1803
87283	1.3665	767
87285	1.0562	454
87289	0.5596	324
87286	0.2293	92
87287	0.1924	71
87288	0.1197	49

Top tissues by expression

243 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	93.07	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.78	gold quality
oocyte	CL:0000023	88.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.85	gold quality
ventricular zone	UBERON:0003053	84.01	gold quality
cartilage tissue	UBERON:0002418	83.59	gold quality
ganglionic eminence	UBERON:0004023	81.75	gold quality
placenta	UBERON:0001987	81.30	gold quality
granulocyte	CL:0000094	80.89	gold quality
stromal cell of endometrium	CL:0002255	80.87	gold quality
leukocyte	CL:0000738	80.75	gold quality
monocyte	CL:0000576	80.64	gold quality
ileal mucosa	UBERON:0000331	80.43	gold quality
right testis	UBERON:0004534	80.25	gold quality
islet of Langerhans	UBERON:0000006	79.77	gold quality
vermiform appendix	UBERON:0001154	79.73	gold quality
testis	UBERON:0000473	79.51	gold quality
epithelial cell of pancreas	CL:0000083	79.48	silver quality
left testis	UBERON:0004533	79.45	gold quality
blood	UBERON:0000178	79.07	gold quality
bone marrow	UBERON:0002371	78.73	gold quality
endometrium	UBERON:0001295	78.51	gold quality
calcaneal tendon	UBERON:0003701	78.50	gold quality
smooth muscle tissue	UBERON:0001135	77.81	gold quality
bone element	UBERON:0001474	77.13	gold quality
omental fat pad	UBERON:0010414	76.71	gold quality
cortical plate	UBERON:0005343	76.69	gold quality
peritoneum	UBERON:0002358	76.67	gold quality
adipose tissue of abdominal region	UBERON:0007808	76.57	gold quality
rectum	UBERON:0001052	76.53	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.60

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

163 targeting ERI1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-5688	99.96	73.23	4504

Literature-anchored findings (GeneRIF, showing 7)

• 3’hExo is a primary candidate for the exonuclease that initiates rapid decay of histone mRNA upon completion and/or inhibition of DNA replication (PMID:14536070)
• molecular cloning; degrades siRNAs in vitro[ERI-1] (PMID:14961122)
• Data describe the structure of the nuclease domain of 3’-5’-exoribonuclease (3’hExo) complexed with rAMP in the presence of magnesium at 1.6 A resolution. (PMID:15451662)
• 3’hExo is a 3’ exonuclease specifically interacting with the 3’ end of histone mRNA (PMID:16912046)
• the crystal structure of a ternary complex of human SLBP RNA binding domain, human 3’hExo, and a 26-nucleotide stem-loop RNA is reported. (PMID:23329046)
• Influenza A virus co-opts ERI1 exonuclease bound to histone mRNA to promote viral transcription. (PMID:32960265)
• Null and missense mutations of ERI1 cause a recessive phenotypic dichotomy in humans. (PMID:37352860)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	eri1	ENSDARG00000044692
mus_musculus	Eri1	ENSMUSG00000031527
rattus_norvegicus	Eri1	ENSRNOG00000011448
caenorhabditis_elegans		WBGENE00000797
caenorhabditis_elegans		WBGENE00001332

Paralogs (2): ERI3 (ENSG00000117419), ERI2 (ENSG00000196678)

Protein

Protein identifiers

3’-5’ exoribonuclease 1 — Q8IV48 (reviewed: Q8IV48)

Alternative names: 3’-5’ exonuclease ERI1, Eri-1 homolog, Histone mRNA 3’-end-specific exoribonuclease, Histone mRNA 3’-exonuclease 1, Protein 3’hExo

All UniProt accessions (6): A0AA34QVV0, A0AA34QVX9, A0AA34QW13, E5RIV7, E5RJM3, Q8IV48

UniProt curated annotations — full annotation on UniProt →

Function. RNA exonuclease that binds to the 3’-end of histone mRNAs and degrades them, suggesting that it plays an essential role in histone mRNA decay after replication. A 2’ and 3’-hydroxyl groups at the last nucleotide of the histone 3’-end is required for efficient 3’-end histone mRNA exonuclease activity and degradation of RNA substrates. Also able to degrade the 3’-overhangs of short interfering RNAs (siRNAs) in vitro, suggesting a possible role as regulator of RNA interference (RNAi). Required for binding the 5’-ACCCA-3’ sequence present in stem-loop structure. Able to bind other mRNAs. Required for 5.8S rRNA 3’-end processing. Also binds to 5.8s ribosomal RNA. Binds with high affinity to the stem-loop structure of replication-dependent histone pre-mRNAs. In vitro, does not have sequence specificity. In vitro, has weak DNA exonuclease activity. In vitro, shows biphasic kinetics such that there is rapid hydrolysis of the last three unpaired RNA nucleotides in the 39 flanking sequence followed by a much slower cleavage through the stem that occurs over a longer incubation period in the order of hours. ERI1-mediated RNA metabolism plays a key role in chondrogenesis.

Subunit / interactions. Identified in a histone pre-mRNA complex, at least composed of ERI1, LSM11, SLBP, SNRPB, SYNCRIP and YBX1. Interacts in a cooperative manner with SLBP to the mature 3’-end of histone mRNAs. Binds to 40S and 60S ribosomal subunits and to 80S assembled ribosomes. Found in a ternary complex with SLBP and the stem-loop structure of the 3’-end of histone mRNAs.

Subcellular location. Cytoplasm. Nucleus. Nucleolus.

Disease relevance. Hoxha-Aliu syndrome (HXAL) [MIM:620662] An autosomal recessive disorder characterized by mild intellectual disability, eyelid ptosis, and limb anomalies including brachydactyly, clinodactyly, dysplastic or absent nails, brachytelephalangy, short metacarpals, and toe syndactyly. The disease is caused by variants affecting the gene represented in this entry. Spondyloepimetaphyseal dysplasia, Guo-Campeau type (SEMDGC) [MIM:620663] An autosomal recessive, severe bone disease characterized by short stature, scoliosis, platyspondyly, irregular vertebral plates, facial dysmorphism, and variable anomalies of the pelvis, hips, and extremities including short, rudimentary, or absent digits. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Although it can bind simultaneously with SLBP to the 3’-end of histone mRNA, the presence of SLBP prevents the exonuclease activity.

Cofactor. Binds 2 magnesium ions per subunit.

Domain organisation. The SAP domain is necessary for binding to the stem-loop structure of histone mRNAs and to form the ternary complex with SLBP, but not for 3’-end histone mRNA exonuclease activity.

RefSeq proteins (4): NP_001341564, NP_001341565, NP_001341567, NP_699163* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003034	SAP_dom	Domain
IPR012337	RNaseH-like_sf	Homologous_superfamily
IPR013520	Ribonucl_H	Domain
IPR036361	SAP_dom_sf	Homologous_superfamily
IPR036397	RNaseH_sf	Homologous_superfamily
IPR047201	ERI-1_3’hExo-like	Domain
IPR051274	3-5_Exoribonuclease	Family

Pfam: PF00929, PF02037

UniProt features (70 total): helix 13, strand 12, sequence variant 11, mutagenesis site 11, binding site 8, turn 4, modified residue 2, domain 2, compositionally biased region 2, active site 2, initiator methionine 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
1W0H	X-RAY DIFFRACTION	1.59
4QOZ	X-RAY DIFFRACTION	2.3
4L8R	X-RAY DIFFRACTION	2.6
1ZBU	X-RAY DIFFRACTION	3
1ZBH	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IV48-F1	86.04	0.77

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 136 (proton acceptor); 293 (proton acceptor)

Ligand- & substrate-binding residues (8): 134; 136; 136; 137; 234; 293; 298; 134

Post-translational modifications (2): 59, 62

Mutagenesis-validated functional residues (11):

Position	Phenotype
92	does not inhibit rna-binding to the stem-loop structure. does not inhibit rna-binding to the stem-loop structure, when a
96	does not inhibit rna-binding to the stem-loop structure.
99	reduces slightly rna-binding to the stem-loop structure.
104	does not inhibit rna-binding to the stem-loop structure. does not inhibit rna-binding to the stem-loop structure, when a
105	inhibits rna-binding to the stem-loop structure.
109	reduces slightly rna-binding to the stem-loop structure; when associated with a-110.
110	reduces slightly rna-binding to the stem-loop structure; when associated with a-109.
111	reduces rna-binding to the stem-loop structure but not 3’-end histone mrna exonuclease activity; when associated with a-
112	reduces rna-binding to the stem-loop structure but not 3’-end histone mrna exonuclease activity; when associated with a-
234	inhibits 3’-end histone mrna exonuclease activity.
235	inhibits rna-binding to the stem-loop structure and 3’-end histone mrna exonuclease activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol

MSigDB gene sets: 456 (showing top): GOBP_RIBOSOME_BIOGENESIS, GOMF_RNA_NUCLEASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_DN, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_MATURATION_OF_5_8S_RRNA_FROM_TRICISTRONIC_RRNA_TRANSCRIPT_SSU_RRNA_5_8S_RRNA_LSU_RRNA, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GOBP_REGULATION_OF_CHROMATIN_ORGANIZATION, GOBP_RRNA_3_END_PROCESSING, GOBP_HISTONE_MRNA_METABOLIC_PROCESS, GOBP_HISTONE_MRNA_CATABOLIC_PROCESS

GO Biological Process (5): maturation of 5.8S rRNA (GO:0000460), exonucleolytic trimming to generate mature 3’-end of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000467), regulatory ncRNA-mediated gene silencing (GO:0031047), rRNA 3’-end processing (GO:0031125), rRNA processing (GO:0006364)

GO Molecular Function (13): 3’-5’-RNA exonuclease activity (GO:0000175), 3’-5’ exonuclease activity (GO:0008408), exoribonuclease II activity (GO:0008859), rRNA binding (GO:0019843), ribosome binding (GO:0043022), metal ion binding (GO:0046872), histone pre-mRNA stem-loop binding (GO:0071207), nucleic acid binding (GO:0003676), RNA binding (GO:0003723), nuclease activity (GO:0004518), exonuclease activity (GO:0004527), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (4): nucleus (GO:0005634), nucleolus (GO:0005730), cytoplasm (GO:0005737), histone pre-mRNA 3’end processing complex (GO:0071204)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
rRNA processing	2
binding	2
maturation of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	1
rRNA 3’-end processing	1
negative regulation of gene expression	1
RNA 3’-end processing	1
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
3’-5’ exonuclease activity	1
RNA exonuclease activity, producing 5’-phosphomonoesters	1
exonuclease activity	1
3’-5’-RNA exonuclease activity	1
RNA binding	1
ribonucleoprotein complex binding	1
cation binding	1
pre-mRNA binding	1
nucleic acid binding	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
hydrolase activity, acting on ester bonds	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1

Protein interactions and networks

STRING

1286 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ERI1	SLBP	Q14493	971
ERI1	DICER1	Q9UPY3	955
ERI1	XRN1	Q8IZH2	889
ERI1	DEDD	O75618	882
ERI1	PIGC	Q92535	830
ERI1	PIGA	P37287	799
ERI1	PIGQ	Q9BRB3	785
ERI1	SYNCRIP	O60506	784
ERI1	PIGH	Q14442	635
ERI1	SIDT1	Q9NXL6	631
ERI1	GTSF1	Q8WW33	615
ERI1	PIGP	P57054	592
ERI1	XRN2	Q9H0D6	591
ERI1	DROSHA	Q9NRR4	584
ERI1	DIS3L2	Q8IYB7	580

IntAct

56 interactions, top by confidence:

A	B	Type	Score
MAGEA10	POTEF	psi-mi:“MI:0914”(association)	0.530
LIN28B	ELAVL2	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
SLBP	ERI1	psi-mi:“MI:0915”(physical association)	0.520
MIF4GD	ERI1	psi-mi:“MI:0915”(physical association)	0.510
ERI1	PHB2	psi-mi:“MI:0915”(physical association)	0.400
Cdc16	ANAPC15	psi-mi:“MI:0914”(association)	0.350
Eif3a	RPSA	psi-mi:“MI:0914”(association)	0.350
Cep78	ING5	psi-mi:“MI:0914”(association)	0.350
CEP170P1	PCYT1A	psi-mi:“MI:0914”(association)	0.350
CDCA5	BDP1	psi-mi:“MI:0914”(association)	0.350
Naa50	WDR46	psi-mi:“MI:0914”(association)	0.350
SYN1	LUC7L3	psi-mi:“MI:0914”(association)	0.350
Ppp2ca	DKFZP586J0619	psi-mi:“MI:0914”(association)	0.350
Topbp1	POP7	psi-mi:“MI:0914”(association)	0.350
Eif3e	RPSA	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
NUDCD1	TUBAL3	psi-mi:“MI:0914”(association)	0.350
LIN28A	MEX3A	psi-mi:“MI:0914”(association)	0.350
DRG1	RPS3A	psi-mi:“MI:0914”(association)	0.350
EIF3G	EIF3CL	psi-mi:“MI:0914”(association)	0.350
RACK1	RPS3A	psi-mi:“MI:0914”(association)	0.350
RPL19	RPS3A	psi-mi:“MI:0914”(association)	0.350
RPS11	SCAMP1	psi-mi:“MI:0914”(association)	0.350
RPS16	MCRIP1	psi-mi:“MI:0914”(association)	0.350
SRP68	RPS3A	psi-mi:“MI:0914”(association)	0.350

BioGRID (49): ERI1 (Affinity Capture-MS), ERI1 (Affinity Capture-MS), ERI1 (Affinity Capture-MS), ERI1 (Affinity Capture-MS), ERI1 (Affinity Capture-MS), ERI1 (Affinity Capture-MS), ERI1 (Affinity Capture-MS), ERI1 (Affinity Capture-MS), ERI1 (Affinity Capture-MS), ERI1 (Affinity Capture-MS), ERI1 (Affinity Capture-MS), ERI1 (Affinity Capture-MS), ERI1 (Affinity Capture-MS), ERI1 (Affinity Capture-RNA), ERI1 (Two-hybrid)

ESM2 similar proteins: A2AQW0, A9JRL3, E1B8U2, E1C3P4, E9Q4Z2, F6HH45, I0IUP4, O00763, P97770, Q08J23, Q149N8, Q1HFZ0, Q1RMU2, Q28E61, Q2T9V5, Q2T9W2, Q3TWN3, Q4V7N2, Q5FVR4, Q5JK52, Q5RED8, Q5T7W7, Q5XH48, Q5ZKK7, Q5ZLV4, Q641K1, Q66H62, Q66IH9, Q6DD21, Q6GR37, Q6NRM6, Q6NS23, Q6ZN16, Q7TMF2, Q7TNK6, Q7TPQ3, Q80TQ2, Q8CE96, Q8H2D5, Q8IV48

Diamond homologs: A6QLH5, A8K979, O43414, O44406, Q08I43, Q10905, Q502M8, Q5BKS4, Q5FVR4, Q5HZL1, Q7TMF2, Q8C460, Q8IV48, Q8W566, Q95RQ4, Q9NG98

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 69 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Eukaryotic Translation Initiation	8	58.8×	2e-11
Cap-dependent Translation Initiation	8	58.8×	2e-11
SARS-CoV-1 modulates host translation machinery	8	58.8×	2e-11
Eukaryotic Translation Elongation	8	53.0×	4e-11
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	8	51.8×	5e-11
Formation of the ternary complex, and subsequently, the 43S complex	9	46.2×	2e-11
Nonsense-Mediated Decay (NMD)	8	44.4×	1e-10
SARS-CoV-2 modulates host translation machinery	8	42.6×	1e-10

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	11	37.7×	1e-12
ribosomal small subunit biogenesis	7	29.5×	4e-07
translation	8	15.2×	4e-06
rRNA processing	5	13.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

136 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	10
Uncertain significance	83
Likely benign	21
Benign	4

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
2674627	NM_153332.4(ERI1):c.893A>C (p.Asp298Ala)	Pathogenic
2674633	NM_153332.4(ERI1):c.582+1G>A	Pathogenic
4082579	NM_153332.4(ERI1):c.627dup (p.Val210fs)	Pathogenic
1686779	NM_153332.4(ERI1):c.401A>G (p.Asp134Gly)	Likely pathogenic
1686780	NM_153332.4(ERI1):c.895T>C (p.Ser299Pro)	Likely pathogenic
2674624	NM_153332.4(ERI1):c.352A>T (p.Lys118Ter)	Likely pathogenic
2674625	NM_153332.4(ERI1):c.450A>T (p.Glu150Asp)	Likely pathogenic
2674626	NM_153332.4(ERI1):c.893A>G (p.Asp298Gly)	Likely pathogenic
2674628	NM_153332.4(ERI1):c.464C>T (p.Pro155Leu)	Likely pathogenic
2674629	NM_153332.4(ERI1):c.62C>A (p.Ser21Ter)	Likely pathogenic
3061999	NM_153332.4(ERI1):c.514C>T (p.Gln172Ter)	Likely pathogenic
586980	NM_153332.4(ERI1):c.627del (p.Lys209_Val210insTer)	Likely pathogenic
976768	NM_153332.4(ERI1):c.730C>T (p.Gln244Ter)	Likely pathogenic

SpliceAI

2288 predictions. Top by Δscore:

Variant	Effect	Δscore
8:9007964:T:A	acceptor_gain	1.0000
8:9007967:TAGG:T	acceptor_loss	1.0000
8:9007968:AG:A	acceptor_gain	1.0000
8:9007969:G:A	acceptor_loss	1.0000
8:9007969:GG:G	acceptor_gain	1.0000
8:9007969:GGA:G	acceptor_gain	1.0000
8:9007969:GGAA:G	acceptor_gain	1.0000
8:9007969:GGAAA:G	acceptor_gain	1.0000
8:9008100:G:GG	donor_gain	1.0000
8:9008105:G:GT	donor_gain	1.0000
8:9008118:C:G	donor_gain	1.0000
8:9011540:A:AG	acceptor_gain	1.0000
8:9011541:G:GG	acceptor_gain	1.0000
8:9011541:GA:G	acceptor_gain	1.0000
8:9011541:GAGGA:G	acceptor_gain	1.0000
8:9011679:G:GT	donor_gain	1.0000
8:9011692:G:GG	donor_gain	1.0000
8:9011753:G:GG	donor_gain	1.0000
8:9020341:A:AG	acceptor_gain	1.0000
8:9020347:T:G	acceptor_gain	1.0000
8:9020347:TAGT:T	acceptor_loss	1.0000
8:9020348:A:AG	acceptor_gain	1.0000
8:9020349:G:GT	acceptor_gain	1.0000
8:9020349:GT:G	acceptor_gain	1.0000
8:9020349:GTT:G	acceptor_gain	1.0000
8:9020349:GTTC:G	acceptor_gain	1.0000
8:9020349:GTTCT:G	acceptor_gain	1.0000
8:9020460:ACAAG:A	donor_loss	1.0000
8:9020461:CAAGG:C	donor_loss	1.0000
8:9020462:AAGGT:A	donor_loss	1.0000

AlphaMissense

2322 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:9011571:T:C	L106P	1.000
8:9011575:A:C	K107N	1.000
8:9011575:A:T	K107N	1.000
8:9020426:T:A	W257R	1.000
8:9020426:T:C	W257R	1.000
8:9020434:T:A	N259K	1.000
8:9020434:T:G	N259K	1.000
8:9029880:C:T	S299F	1.000
8:9008112:T:C	L84P	0.999
8:9011543:G:A	G97R	0.999
8:9011543:G:C	G97R	0.999
8:9011544:G:A	G97E	0.999
8:9011559:T:C	L102P	0.999
8:9011568:G:C	R105T	0.999
8:9011569:A:C	R105S	0.999
8:9011569:A:T	R105S	0.999
8:9011573:A:G	K107E	0.999
8:9011574:A:T	K107I	0.999
8:9011655:A:C	D134A	0.999
8:9011655:A:T	D134V	0.999
8:9011656:C:A	D134E	0.999
8:9011656:C:G	D134E	0.999
8:9011662:A:C	E136D	0.999
8:9011662:A:T	E136D	0.999
8:9011663:G:C	A137P	0.999
8:9011706:T:A	I151K	0.999
8:9011706:T:G	I151R	0.999
8:9011724:T:A	V157D	0.999
8:9016344:T:A	V174E	0.999
8:9016376:T:C	F185L	0.999

dbSNP variants (sampled 300 via entrez): RS1000030615 (8:9011298 G>A,C), RS1000084605 (8:9068595 C>G), RS1000088594 (8:9047581 C>T), RS1000100816 (8:9023628 A>G), RS1000105873 (8:9071251 T>C), RS1000118029 (8:9063397 G>A,C,T), RS1000133579 (8:9074934 C>A,G), RS1000157615 (8:9073559 A>T), RS1000194271 (8:9019707 T>G), RS1000196375 (8:9013521 C>G,T), RS1000233221 (8:9053457 T>C), RS1000240350 (8:9043810 C>G,T), RS1000249209 (8:9021754 C>A,T), RS1000311821 (8:9045434 C>T), RS1000325335 (8:9098753 A>G)

Disease associations

OMIM: gene MIM:608739 | disease phenotypes: MIM:620663, MIM:620662

GenCC curated gene-disease

Disease	Classification	Inheritance
Hoxha-Aliu syndrome	Strong	Autosomal recessive
spondyloepimetaphyseal dysplasia, Guo-Campeau type	Strong	Autosomal recessive

Mondo (4): spondyloepimetaphyseal dysplasia, Guo-Campeau type (MONDO:0958006), Hoxha-Aliu syndrome (MONDO:0958005), primary amenorrhea (MONDO:1060208), renal agenesis, unilateral (MONDO:0019636)

Orphanet (1): Renal agenesis, unilateral (Orphanet:93100)

HPO phenotypes

102 total (30 of 102 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000076	Vesicoureteral reflux
HP:0000126	Hydronephrosis
HP:0000218	High palate
HP:0000220	Velopharyngeal insufficiency
HP:0000243	Trigonocephaly
HP:0000248	Brachycephaly
HP:0000268	Dolichocephaly
HP:0000286	Epicanthus
HP:0000294	Low anterior hairline
HP:0000307	Pointed chin
HP:0000325	Triangular face
HP:0000341	Narrow forehead
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000378	Cupped ear
HP:0000400	Macrotia
HP:0000431	Wide nasal bridge
HP:0000465	Webbed neck
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000520	Proptosis
HP:0000545	Myopia
HP:0000582	Upslanted palpebral fissure
HP:0000717	Autism
HP:0000750	Delayed speech and language development
HP:0000767	Pectus excavatum

GWAS associations

69 associations (top):

Study	Trait	p-value
GCST002481_5	Acne (severe)	9.000000e-07
GCST004616_193	Platelet distribution width	4.000000e-41
GCST004630_265	Mean corpuscular hemoglobin	1.000000e-11
GCST004946_170	Schizophrenia	2.000000e-08
GCST005232_114	Neuroticism	2.000000e-29
GCST005232_129	Neuroticism	3.000000e-31
GCST006190_44	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	5.000000e-06
GCST006192_31	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	1.000000e-08
GCST006192_65	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	1.000000e-09
GCST006193_27	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-06
GCST006195_57	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	3.000000e-09
GCST006195_8	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-08
GCST007565_174	Morning person	9.000000e-14
GCST007709_217	General factor of neuroticism	9.000000e-09
GCST007928_98	Medication use (diuretics)	1.000000e-14
GCST010002_269	Refractive error	1.000000e-24
GCST010132_13	Processed meat consumption	5.000000e-09
GCST010132_6	Processed meat consumption	5.000000e-11
GCST010142_4	Fish- and plant-related diet	2.000000e-12
GCST010142_6	Fish- and plant-related diet	3.000000e-12
GCST010142_63	Fish- and plant-related diet	2.000000e-12
GCST010142_67	Fish- and plant-related diet	1.000000e-10
GCST010142_70	Fish- and plant-related diet	8.000000e-10
GCST010142_89	Fish- and plant-related diet	4.000000e-16
GCST010142_90	Fish- and plant-related diet	7.000000e-15
GCST010703_306	Brain morphology (MOSTest)	5.000000e-26
GCST011908_4	Bipolar disorder (early vs late onset)	1.000000e-07
GCST012226_493	Waist circumference adjusted for body mass index	4.000000e-14
GCST012226_494	Waist circumference adjusted for body mass index	4.000000e-10
GCST012226_495	Waist circumference adjusted for body mass index	2.000000e-15

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0007984	platelet component distribution width
EFO:0004527	mean corpuscular hemoglobin
EFO:0007660	neuroticism measurement
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0006335	systolic blood pressure
EFO:0008328	chronotype measurement
EFO:0009928	Diuretic use measurement
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0009963	bipolar I disorder
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007991	eosinophil percentage of leukocytes
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

30 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases expression	3
Nickel	increases expression	2
trichostatin A	affects expression	1
sodium arsenite	increases abundance, affects cotreatment, decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
avobenzone	increases expression	1
tanespimycin	affects cotreatment, increases expression	1
ICG 001	increases expression	1
VER 155008	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Vorinostat	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance, affects cotreatment	1
Benzo(a)pyrene	affects methylation	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Diazinon	increases methylation	1
Diuron	decreases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Phthalic Acids	decreases methylation	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	increases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

2 cell lines: 1 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D7PM	Ubigene A-549 ERI1 KO	Cancer cell line	Male
CVCL_D9EJ	Ubigene HEK293 ERI1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

2 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT07164248	Not specified	COMPLETED	Evaluation of Bone Mineral Density Indications and Outcomes in Female Adolescents: Implications for Early Detection of Osteopenia/Osteoporosis and Gynecologic Practice
NCT01831141	Not specified	UNKNOWN	Long Term Outcome of Congenital Solitary Kidney